Overcoming Challenges with Multiple Clinical Outcome Assessments in a Rare Neurodegenerative Clinical Trial

By Danit Ben Avraham (Senior Project Director, Global Project Leadership at Allucent) and Gilad Rosenberg, MD (Executive Director, Therapeutic Area Medical Lead, Neuroscience at Allucent)

Background

Allucent was selected to perform a full-service Phase 1/2a, open-label basket trial with multiple ascending doses across patient cohorts diagnosed with rare neurodegenerative disorders. Due to the complex nature of the study design and patient populations being treated, Clinical Outcome Assessments (COAs) were necessary to comprehensively evaluate treatment impact.

Patient Population: Over 80 patients across multiple cohorts with certain rare neurodegenerative disorders

Countries/Total Sites: 16 sites in six countries across UK, EU, and MENA.

Clinical Outcome Assessment and Patient Recruitment Challenges in Multi-Cohort Study Design

A central challenge in executing studies utilizing multiple paper and electronic clinical outcome assessments, is ensuring consistency and reliability in clinician-reported outcomes, particularly when assessments are rater-dependent. Variability in rater qualifications and clinical experience, ranging from expert clinicians to novice allied health professionals, can introduce significant inter- and intra-rater discrepancies. Traditional training approaches, such as passive reading or video modules, are often insufficient for preparing raters to administer assessments accurately and consistently. These limitations are exacerbated by site staff turnover, which demands the continuous implementation of adaptive training programs.

Ensuring timely and standardized training becomes even more challenging when tied to the licensing and setup of electronic Clinical Outcome Assessment (eCOA) platforms. Delays in platform access, user credentialing, and software licensing can directly impact training schedules and site readiness, creating downstream risks to data quality and study timelines.

As with many of today’s complex neurodegenerative clinical trial protocols, this study incorporated a critical imaging component alongside a range of intricate procedures, such as the collection and processing of diverse fluid biomarkers from both blood and cerebrospinal fluid (CSF). Successfully executing such protocols demands seamless cross-functional coordination to ensure consistency and standardization across all participating sites.

Additionally, this study faced an ongoing challenge in patient recruitment for a multi-cohort clinical study in maintaining a consistent and compliant waiting list while preventing premature screening. Sites were eager to enroll participants, but due to staggered cohort activations and pending regulatory approvals, it was critical that no patients were screened or assessed prior to official cohort activation.

Strategic Solutions Navigating Clinical Outcome Assessments and Patient Recruitment

To address the challenges associated with Clinical Outcome Assessments (COAs) in this study, several strategic solutions were implemented:

• Clear and ongoing communication between Allucent, the sponsor, and COA providers was essential to align expectations, avoid missteps, and ensure efficient setup.
• Allucent was directly involved in protocol development, which allowed for early clarification on what COA components were mandatory versus optional, which helped to prevent scope creep and streamline execution.
• All requirements were confirmed and agreed upon prior to protocol finalization to ensure alignment among all stakeholders.
• Timelines were carefully planned from the outset, recognizing the time needed to coordinate licensing agreements, secure contracts, and ensure availability of validated translations in all necessary languages or, where translations were missing, to obtain COA owner approval for new ones.
• When COA providers were not part of Allucent’s pre-qualified vendor list, the sponsor proactively managed contracting to avoid administrative delays.

These coordinated efforts ensured a smoother implementation of COAs and helped maintain both data integrity and study timelines.

In response to the complexity of the study protocol, including imaging requirements and collection and processing of diverse fluid biomarkers from both blood and CSF, comprehensive imaging manuals and guidelines were implemented. This facilitated standardized training and enabled timely coordination between site radiology departments and the central imaging lab, supporting consistency and protocol adherence across all sites.

To address the patient recruitment challenges in this multi-cohort study, a comprehensive and proactive approach was implemented through the development of a Cohort Management and Recruitment Strategy Plan. This plan outlined targeted recruitment and retention strategies, identified potential barriers, and detailed mitigation activities.

Recognizing the rarity of the indications and the fact that patients were already known to the sites, sites were instructed to identify and line up potential participants in advance, even prior to the Site Initiation Visit (SIV). These patients were added to a carefully maintained waiting list for future cohort enrollment, ensuring preparedness without initiating premature screening. To reinforce compliance, a Slot Reservation Form was required for each patient before screening could occur. This form was reviewed and approved by Allucent and the sponsor to ensure alignment with cohort-specific timelines and regulatory readiness.

Additionally, strict timelines for iDMC (Independent Data Monitoring Committee) reviews were agreed upon in advance to facilitate smooth transitions between dose cohorts and prevent unnecessary delays in patient enrollment. This structured and collaborative approach helped maintain protocol compliance while maximizing recruitment efficiency.

Operational Outcomes: From Startup to First Patient In (FPI)

Although the study is ongoing, the early implementation of targeted strategies has already produced measurable operational benefits. The proactive approach to Clinical Outcome Assessment (COA) planning—emphasizing early collaboration among Allucent, the sponsor, and COA providers—has led to improved clarity around protocol expectations, streamlined vendor contracting, and minimized delays related to licensing and translation requirements. Similarly, the recruitment challenges posed by a multi-cohort design in rare neurological patient populations were mitigated through the creation of a robust Cohort Management and Recruitment Strategy Plan, resulting in First Patient In (FPI) being achieved on schedule. By establishing clear processes for patient waiting lists, slot reservation, and iDMC review timelines, sites have been able to prepare effectively for upcoming cohorts while maintaining compliance.

These early successes suggest that the study is well-positioned to meet its long-term recruitment and operational goals. Continued monitoring and adaptation will be critical as the study progresses toward full enrollment and data collection milestones.

To learn more about Allucent’s expertise in supporting patient recruitment in neurodegenerative clinical trials, visit our website, Neuroscience CRO for Psychiatric & Neurology Clinical Trials.